Synergistic anti-inflammatory effects of luteolin and chicoric acid, two abundant constituents of the common dandelion (Taraxacum officinale Weber), were investigated in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Co-treatment with luteolin and chicoric acid synergistically reduced cellular concentrations of nitric oxide (NO) and prostaglandin E2 (PGE2) and also inhibited expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, co-treatment reduced the levels of proinflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. Both luteolin and chicoric acid suppressed oxidative stress, but they did not exhibit any synergistic activity. Luteolin and chicoric acid co-treatment inhibited phosphorylation of NF-κB and Akt, but had no effect on extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. This anti-inflammatory signaling cascade coincides with that affected by luteolin treatment alone. These results suggest that luteolin plays a central role in ameliorating LPS-induced inflammatory cascades via inactivation of the NF-κB and Akt pathways, and that chicoric acid strengthens the anti-inflammatory activity of luteolin through NF-κB attenuation.